May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

INTRODUCTION: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. METHODS: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. RESULTS: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). CONCLUSIONS: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Arterial Hypertension and the Hidden Disease of the Eye: Diagnostic Tools and Therapeutic Strategies.

Hypertension is a major cardiovascular risk factor that is responsible for a heavy burden of morbidity and mortality worldwide. A critical aspect of cardiovascular risk estimation in hypertensive patients depends on the assessment of hypertension-mediated organ damage (HMOD), namely the generalized structural and functional changes in major organs induced by persistently elevated blood pressure values. The vasculature of the eye shares several common structural, functional, and embryological features with that of the heart, brain, and kidney. Since retinal microcirculation offers the unique advantage of being directly accessible to non-invasive and relatively simple investigation tools, there has been considerable interest in the development and modernization of techniques that allow the assessment of the retinal vessels' structural and functional features in health and disease. With the advent of artificial intelligence and the application of sophisticated physics technologies to human sciences, consistent steps forward have been made in the study of the ocular fundus as a privileged site for diagnostic and prognostic assessment of diverse disease conditions. In this narrative review, we will recapitulate the main ocular imaging techniques that are currently relevant from a clinical and/or research standpoint, with reference to their pathophysiological basis and their possible diagnostic and prognostic relevance. A possible non pharmacological approach to prevent the onset and progression of retinopathy in the presence of hypertension and related cardiovascular risk factors and diseases will also be discussed.

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD).

Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate that IL6 rs180795 and MIF rs755622 SNPs might be markers of genetic susceptibility to ESRD. In particular, the C positive genotypes of MIF rs755622, (dominant model) seem to be an independent risk factor for ESDR patients (data adjusted for age, gender, and associated pathologies). Stratifying results according to age MIF rs755622 C positive genotype frequencies are increased in both the two age classes considered (<59 and ≥59-year-old subjects). Analyses of data according to gender allowed us to observe that ESRD women shoved a significantly reduced frequency of genotypes bearing IL6 rs180795 C allele. In addition, MIF rs755622 might interact with diabetes or hypercholesterolemia in increasing susceptibility to ESRD. In conclusion, our data indicate that some polymorphisms involved in the regulation of both renal function and inflammatory response can influence the evolution of chronic kidney disease and suggest that the modulation of the activities of these and other genes should also be considered as therapeutic targets on to intervene with innovative therapies.

Resistive index of ophthalmic artery as an imaging biomarker of hypertension-related vascular and kidney damage.

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro- and microcirculation in vivo. RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

Should reduction of increased short-term blood pressure variability be a target of antihypertensive therapy?

It has long been known that blood pressure (BP) is characterized by marked short-term fluctuations occurring within a 24-h period and also by long-term oscillations occurring over more prolonged periods of time. An increased short-term blood pressure variability (BPV) appears to importantly contribute to target organ damage and to the enhanced cardiovascular risk of hypertensive patients, over and above the effect of an increase in mean BP levels. Reducing 24-h mean BP is the main aim of antihypertensive therapy, but initial data are available that additional cardiovascular protection can be achieved by reducing BPV. However, to definitively prove the prognostic role of short-term BPV and the need for its control by treatment, evidence is still needed from intervention trials aimed at demonstrating that by reducing BPV through administration of antihypertensive drugs, a reduction in organ damage and in the rate of cardiovascular events can be obtained.

Relationship of choroidal thickness with pulsatile hemodynamics in essential hypertensive patients.

Controversy exists about the association of choroidal thickness (CTh) with blood pressure (BP) values. There is some evidence suggesting that central hemodynamics changes are associated with microvascular disease. Our study was aimed to assess the relationships between CTh and clinic and 24-h BP and between CTh and estimated 24-h aortic pulse pressure (aPP), 24-h aortic systolic BP (aSBP), and 24-h aortic augmentation index (aAIx) in a group of hypertensive patients. We enrolled 158 hypertensive subjects (mean age 48 ± 13 years) all of which underwent evaluation of the choroidal district by Swept-Source optical coherence tomography (SS-OCT) and 24-h BP monitoring, in order to measure peripheral BP and to estimate central hemodynamic parameters. Inverse significant correlations of clinic PP, 24-h aPP, 24-h aSBP, and 24-h aAIx with thicknesses of central ring, inner ring, and outer ring of the choroid and its overall average were found. The strongest of these correlations was that relating 24-h aPP with overall average choroidal thickness (r = -.531; P < .001). When we divided the study population in subjects with 24-h aPP above and below the median value (35 mm Hg), CTh were thinner in subjects with higher values of 24-aPP as compared to those with lower ones, even after adjustment for age, and other potential confounders. The relationships of CTh with 24-h aPP remained significant also taking into account the effects of various covariates in linear multiple regression analyses. Our findings support the concept of a cross-talk between macro- and microcirculation.

Choroidal thickness is associated with renal hemodynamics in essential hypertension.

The choroid is the most vascularized structure of the eye and plays a central role in the development of the retinal vascular changes that occur in arterial hypertension. Changes of choroidal thickness (ChT) assessed by optical coherence tomography (OCT) technology could reflect the vascular complications of hypertension. Also, intrarenal hemodynamic damage, associated with endothelial dysfunction, demonstrated to be a good indicator of systemic morphofunctional arterial impairment. The aim of this study is to assess the relationship between ChT and renal hemodynamics in subjects with essential hypertension. Routine laboratory tests, clinical history, and physical examination, including blood pressure assessment, were performed in 90 subjects with essential hypertension. All patients underwent Doppler ultrasonographic evaluation of intra-renal hemodynamics and OCT imaging to assess ChT. When subjects were divided in two groups based on renal resistive index (RRI), group I (RRI ≥ 75% percentile) showed significantly lower values of ChT than group II (RRI < 75% percentile) (P < .001). When divided in two groups based on the ChT median values, patients with lower ChT had significantly higher RRI values than those with ChT above the median values (P < .05). In multivariate model including age, eGFR, and other variables as confounding factors, RRI ≥ 75% was independently associated with ChT. ChT was significantly correlated with renal resistive index in subjects with essential hypertension, confirmed in multivariate analyses. This result could be referred to changes in vascular elastic properties that occur in retinal and intrarenal vascular system probably due to oxidative stress and endothelial dysfunction commonly found in early complications of hypertension.

Relationship of a Body Shape Index and Body Roundness Index with carotid atherosclerosis in arterial hypertension.

BACKGROUND AND AIMS: A Body Shape Index (ABSI) and Body Roundness Index (BRI) are two new anthropometric adiposity indices that have shown to be associated better than BMI with adipose abdominal tissue, with the onset of diabetes and the risk of premature death. Little is known about the influence of ABSI and BRI on subclinical vascular damage. The study was aimed to assess the relationship between ABSI and BRI with carotid atherosclerosis damage in subjects with arterial hypertension. METHODS AND RESULTS: A total of 468 patients with arterial hypertension (30-80 years old) were enrolled; adiposity indices were calculated (BMI, WC, ABSI, BRI) and carotid ultrasonographic examination was performed to detect atherosclerotic damage (IMT or atherosclerotic plaque). BRI, but not ABSI, was higher in subjects with IMT> 0.90 mm in comparison to those with a lower IMT (p < 0.001), whereas patients with carotid plaques showed higher values of ABSI (p = 0.001), as well as of BRI (p = 0.003). Linear regression analysis disclosed significant correlation of IMT with ABSI, BRI and BMI (all p < 0.001). In the multivariate analysis, BRI was independently correlated with cIMT (p = 0.015). On the contrary, ABSI did not show any independent association with cIMT. However, ABSI was strongly associated with carotid plaques in multiple logistic regression analysis after adjustment for potential confounding factors. When BRI or BMI replaced ABSI into the multivariate models, they did not show any independent correlation with carotid plaques. CONCLUSIONS: ABSI may be proposed as a better correlate of carotid atherosclerosis than the traditional measures of adiposity.

Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease.

Intrarenal hemodynamic alterations are independent predictors of cardiovascular events in different populations. It has been hypothesized that there is an association between renal hemodynamics and coronary atherosclerotic burden in patients with hypertension. Therefore, the present study examined the associations between renal hemodynamics, coronary atherosclerotic burden and carotid atherosclerotic disease. A total of 130 patients with hypertension aged between 30-80 years who had been referred for an elective coronary angiography were enrolled in the present study. A duplex ultrasound of the intrarenal vasculature was performed to evaluate the resistive index (RI), pulsatility index (PI) and acceleration time (AT). The carotid intima-media thickness was additionally assessed. A coronary angiography was performed to detect the atherosclerotic burden using the Gensini Score (GS). Based on the GS values, subjects were divided into quintiles (I: ≤9; II: 9-17; III: 17-30; IV: 30-44; and V: GS >44) as well as in subjects with mild (GS ≤30) or severe coronary disease (GS >30). A weak significant difference in PI was identified among quintiles (P=0.041), whereas, RI and AT did not differ significantly. PI was associated with GS in the group with low coronary atherosclerotic burden (GS ≤30; P=0.047), whereas, no association was detected in subjects with GS >30. This association remained following adjustment for age and left ventricular ejection fraction (P=0.025). In conclusion, renal vascular alterations were associated with coronary atherosclerotic burden in patients with hypertension with mild coronary disease.

The Unsolved Conundrum of Optimal Blood Pressure Target During Acute Haemorrhagic Stroke: A Comprehensive Analysis.

Intracerebral haemorrhage (ICH) is a devastating cerebrovascular disease, which accounts to 15% of all strokes. Among modifiable risk factors for ICH, hypertension is the most frequent. High blood pressure (BP) is detected in more than 75-80% of patients with ICH. Extremely elevated BP has been associated with early hematoma growth, a relatively frequent occurrence and powerful predictor of poor outcome in patients with spontaneous ICH. On the other hand, excessively low BP might cause cerebral hypoperfusion and ultimately lead to poor outcome. This review will analyse the most important trials that have tried to establish how far should BP be lowered during acute ICH. These trials have demonstrated either a small non-significant benefit (INTERACT-2, INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial) or no benefit (ATACH-2, Antihypertensive treatment of acute cerebral haemorrhage II study) when intensive systolic BP reduction was compared with modest or standard BP reduction. The more recent meta-analyses including studies investigating this issue yielded similar conclusions: aggressive BP control in the acute phase of ICH is not beneficial. For these reasons the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the management of arterial hypertension, do not recommend treatment to immediately lower BP in patients with acute ICH and systolic BP < 220 mmHg. Careful lowering of SBP to less than 180 mmHg via i.v. Infusion may be considered only in patients with SBP ≥ 220 mmHg.

Inflammation and Aortic Pulse Wave Velocity: A Multicenter Longitudinal Study in Patients With Inflammatory Bowel Disease.

Background Inflammatory bowel disease ( IBD ) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse-wave velocity ( aPWV ), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti-TNFa (anti-tumor necrosis factor-alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5-5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti-TNFa during follow-up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates ( P=0.01). Disease duration ( P=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high-sensitivity C-reactive protein during follow-up ( P=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti-TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow-up ( P=0.85). Conclusions Long-term anti-TNFa therapy reduces aPWV , an established surrogate measure of cardiovascular risk, in patients with IBD . This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.

Association between early-stage chronic kidney disease and reduced choroidal thickness in essential hypertensive patients.

The introduction in the past few years of advanced optical coherence tomography (OCT) techniques has greatly increased our understanding of the choroid, which is the most important vascular layer of the eye. Our study aimed to assess choroidal thickness by using swept-source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without early-stage chronic kidney disease (CKD). We enrolled 100 EHs, of whom 65 were without kidney damage, and 35 had stage 1-3 CKD. In all of the participants, SS-OCT and a routine biochemical workup were performed. Glomerular filtration rate (GFR) was estimated by the CKD Epidemiology Collaboration equation (eGFR). CKD was defined in agreement with the Kidney Disease Outcomes Quality Initiative Kidney Disease: Improving Global Outcomes 2002 guidelines. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, which divides the macula into nine subfields. The circular grid consists of three concentric rings. EHs with CKD showed thinner choroidal thicknesses than those without it (all p < 0.05), even after adjustment for potential confounding factors. Overall choroidal thickness correlated significantly and directly with eGFR (r = 0.36) and negatively with urinary albumin excretion (r = -0.39). The association of choroidal thickness with CKD was confirmed in multiple logistic regression analyses once the effects of age and other confounding variables were accounted for. The odds ratio of having early-stage CKD associated with a standard deviation increase in overall choroidal thickness was 0.43 (0.24-0.75, 95% confidence interval; p = 0.007). In conclusion, our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction.